Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-Butylidenephthalide
Phthalides are bioactive compounds that naturally occur in the family Apiaceae. Considering their potentially versatile applications, it is desirable to determine their physical properties, activity and metabolic pathways. This study aimed to examine the utility of whole-cell biocatalysts for obtain...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-07-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/14/7600 |
| _version_ | 1797526923269636096 |
|---|---|
| author | Joanna Gach Teresa Olejniczak Piotr Krężel Filip Boratyński |
| author_facet | Joanna Gach Teresa Olejniczak Piotr Krężel Filip Boratyński |
| author_sort | Joanna Gach |
| collection | DOAJ |
| description | Phthalides are bioactive compounds that naturally occur in the family Apiaceae. Considering their potentially versatile applications, it is desirable to determine their physical properties, activity and metabolic pathways. This study aimed to examine the utility of whole-cell biocatalysts for obtaining 3-butyl-3-hydroxyphthalide, which is the metabolite formulated during mammalian metabolism of 3-<i>n</i>-butylidenephthalide. We performed transformations using 10 strains of fungi, five of which efficiently produced 3-butyl-3-hydroxyphthalide. The product yield, determined by high-performance liquid chromatography, reached 97.6% when <i>Aspergillus candidus</i> AM 386 was used as the biocatalyst. Increasing the scale of the process resulted in isolation yields of 29–45% after purification via reversed-phase thin layer chromatography, depending on the strain of the microorganism used. We proposed different mechanisms for product formation; however, hydration of 3-<i>n</i>-butylidenephthalide seems to be the most probable. Additionally, all phthalides were tested against clinical strains of <i>Candida albicans</i> using the microdilution method. Two phthalides showed a minimum inhibitory concentration, required to inhibit the growth of 50% of organisms, below 50 µg/mL. The 3-<i>n</i>-butylidenephthalide metabolite was generally inactive, and this feature in combination with its low lipophilicity suggests its involvement in the detoxification pathway. The log <i>P</i> value of tested compounds was in the range of 2.09–3.38. |
| first_indexed | 2024-03-10T09:36:13Z |
| format | Article |
| id | doaj.art-5ab6e8917b254114ac7d07f70ae215b7 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T09:36:13Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5ab6e8917b254114ac7d07f70ae215b72023-11-22T04:01:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012214760010.3390/ijms22147600Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-ButylidenephthalideJoanna Gach0Teresa Olejniczak1Piotr Krężel2Filip Boratyński3Department of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandDepartment of Chemistry, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, PolandPhthalides are bioactive compounds that naturally occur in the family Apiaceae. Considering their potentially versatile applications, it is desirable to determine their physical properties, activity and metabolic pathways. This study aimed to examine the utility of whole-cell biocatalysts for obtaining 3-butyl-3-hydroxyphthalide, which is the metabolite formulated during mammalian metabolism of 3-<i>n</i>-butylidenephthalide. We performed transformations using 10 strains of fungi, five of which efficiently produced 3-butyl-3-hydroxyphthalide. The product yield, determined by high-performance liquid chromatography, reached 97.6% when <i>Aspergillus candidus</i> AM 386 was used as the biocatalyst. Increasing the scale of the process resulted in isolation yields of 29–45% after purification via reversed-phase thin layer chromatography, depending on the strain of the microorganism used. We proposed different mechanisms for product formation; however, hydration of 3-<i>n</i>-butylidenephthalide seems to be the most probable. Additionally, all phthalides were tested against clinical strains of <i>Candida albicans</i> using the microdilution method. Two phthalides showed a minimum inhibitory concentration, required to inhibit the growth of 50% of organisms, below 50 µg/mL. The 3-<i>n</i>-butylidenephthalide metabolite was generally inactive, and this feature in combination with its low lipophilicity suggests its involvement in the detoxification pathway. The log <i>P</i> value of tested compounds was in the range of 2.09–3.38.https://www.mdpi.com/1422-0067/22/14/7600biotransformationsApiaceaebioactivityphthalideslipophilicitylactones |
| spellingShingle | Joanna Gach Teresa Olejniczak Piotr Krężel Filip Boratyński Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-Butylidenephthalide International Journal of Molecular Sciences biotransformations Apiaceae bioactivity phthalides lipophilicity lactones |
| title | Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-Butylidenephthalide |
| title_full | Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-Butylidenephthalide |
| title_fullStr | Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-Butylidenephthalide |
| title_full_unstemmed | Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-Butylidenephthalide |
| title_short | Microbial Synthesis and Evaluation of Fungistatic Activity of 3-Butyl-3-hydroxyphthalide, the Mammalian Metabolite of 3-<i>n</i>-Butylidenephthalide |
| title_sort | microbial synthesis and evaluation of fungistatic activity of 3 butyl 3 hydroxyphthalide the mammalian metabolite of 3 i n i butylidenephthalide |
| topic | biotransformations Apiaceae bioactivity phthalides lipophilicity lactones |
| url | https://www.mdpi.com/1422-0067/22/14/7600 |
| work_keys_str_mv | AT joannagach microbialsynthesisandevaluationoffungistaticactivityof3butyl3hydroxyphthalidethemammalianmetaboliteof3inibutylidenephthalide AT teresaolejniczak microbialsynthesisandevaluationoffungistaticactivityof3butyl3hydroxyphthalidethemammalianmetaboliteof3inibutylidenephthalide AT piotrkrezel microbialsynthesisandevaluationoffungistaticactivityof3butyl3hydroxyphthalidethemammalianmetaboliteof3inibutylidenephthalide AT filipboratynski microbialsynthesisandevaluationoffungistaticactivityof3butyl3hydroxyphthalidethemammalianmetaboliteof3inibutylidenephthalide |